The general problem area to be investigated is the nature and role of transmembrane interactions of the extracellular matrix and the cytoskeleton in normal and transformed cells. The long term objective is to provide a deeper understanding at the molecular level of the protein-protein interactions, transmembrane connections and signals involved in (1) cell attachment to substrata especially extracellular matrix proteins (2) cytoskeletal organization and associations with the plasma membrane (3) the development of normal cell morphologies and behaviors. Alterations in these processes are an important part of the malignant phenotype and we expect that more detailed understanding of them in normal cells will provide insights into the development of malignant behavior in oncogenically transformed cells. Specific topics to be investigated include: 1. The derivation, and effects upon cell behavior, of alternatively spliced forms of fibronectin. 2.The effects of laminin on development of polarized cell morphology in neurons. 3.The roles of various integrins in interactions with fibronectin, laminin and the cytoskeleton. 4.The interactions of several cytoskeletal proteins with membranes. These proteins include talin, ezrin/p8l and myosins 1. 5.The interactions of talin and ezrin with other cytoskeletal and cytoplasmic constituents. A variety of normal cell types as well as oncogenically transformed cells will be studied in order to investigate hypotheses concerning the roles of these proteins in normal cell function and alterations produced by oncogenic transformation. Molecular and cellular biological approaches will be applied to address these questions.